Forschungszentrum DZNE4h ago
New paper out: rTCT: Rodent Triangle Completion Task to Facilitate Reverse Translational Study of Path Integration.: Duncan, Stephen; Rehman, Sulaiman; Segen, Vladislava; et al.
Hippocampus Vol. 36, no. 3, p. e70090 http://dlvr.it/TS6f2T | Please share #dzne #papers
rTCT: Rodent Triangle Completion Task to Facilitate Reverse Translational Study of Path Integration. - DZNEPUB

Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimer's disease. In rodents, however, path integration is assessed using a wide variety of tasks, but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study, we developed and tested a novel rodent version of the triangle completion task to enhance cross-species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimer's disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration. Duncan, Stephen; Rehman, Sulaiman; Segen, Vladislava; Choi, Irene; Lawrence, Sami; Kalani, Om; Gold, Lisette; Goldman, Lillian; Ramlo, Sophia; Stickel, Kylene; Layfield, Dylan; Wolbers, Thomas; Tiganj, Zoran; Newman, Ehren L

Forschungszentrum DZNE8h ago
New paper out: Midsagittal Midbrain Area and Midbrain-to-Pons-Ratio Cannot Distinguish Overlap Syndromes Between Amyotrophic Lateral Sclerosis and Progressive Supranuclear Palsy.: Cantré, Daniel; König, Jochem; Makowsky, Caroline; et al.
Clinical neuroradiology Vol. 36, no. 1, p. 161 - 168 http://dlvr.it/TS6Vkt | Please share #dzne #papers
Midsagittal Midbrain Area and Midbrain-to-Pons-Ratio Cannot Distinguish Overlap Syndromes Between Amyotrophic Lateral Sclerosis and Progressive Supranuclear Palsy. - DZNEPUB

When amyotrophic lateral sclerosis (ALS), a TDP-43 proteinopathy, and progressive supranuclear palsy (PSP), a tauopathy, are associated with frontotemporal dementia (ALS-FTD or PSP-FTD), clinical differentiation can be challenging. There are no established imaging biomarkers to differentiate ALS-FTD from PSP-FTD.We evaluated the midsagittal midbrain area (MBA) and the midbrain-to-pons-(MB/P)-ratios in T1 MPRAGE MRI of 36 PSP cases (n = 14 PSP-FTD), 77 ALS cases (n = 10 ALS-FTD), and 72 healthy controls (HC).In ALS, both parameters were indistinguishable from HC. Patients with ALS-FTD had low MBA-values and MB/P-ratios not significantly different from cases of PSP. While ROC-analyses provided an excellent diagnostic accuracy of both parameters for differentiating PSP from HC (AUCMBA = 0.974) as well as PSP from ALS (AUCMBA = 0.982), midbrain morphometry provided poor diagnostic accuracy for distinguishing ALS-FTD from PSP-FTD (AUCMBA = 0,614).The MBA and the MB/P-ratio are morphometric parameters that have proven reliable in atypical Parkinsonian syndromes. Both can distinguish between PSP and ALS in their typical clinical forms. However, they cannot differentiate between PSP-FTD and ALS-FTD. Cantré, Daniel; König, Jochem; Makowsky, Caroline; Dyrba, Martin; Prudlo, Johannes

Forschungszentrum DZNE1d ago
New paper out: Reply to: Utility of Progression Rate Since Symptom Onset in Predicting Subsequent Survival in Progressive Supranuclear Palsy.: Quattrone, Andrea; Franzmeier, Nicolai; Höglinger, Günter U
Movement disorders Vol. 41, no. 1, p. 279 - 280 http://dlvr.it/TS6285 | Please share #dzne #papers
Reply to: Utility of Progression Rate Since Symptom Onset in Predicting Subsequent Survival in Progressive Supranuclear Palsy. - DZNEPUB

Quattrone, Andrea; Franzmeier, Nicolai; Höglinger, Günter U

Forschungszentrum DZNE1d ago
New paper out: Cost-Effectiveness Modelling of Multiple System Atrophy for Early Health Technology Assessment.: Grand, Tobias Sydendal; Ren, Shijie; Thokala, Praveen; et al.
PharmacoEconomics - open Vol. 10, no. 1, p. 179 - 196 http://dlvr.it/TS5t8L | Please share #dzne #papers
Cost-Effectiveness Modelling of Multiple System Atrophy for Early Health Technology Assessment. - DZNEPUB

Multiple system atrophy is a neurodegenerative and rapidly progressing disease. Although symptoms often overlap, diagnostic criteria define two motor phenotypes: cerebellar and Parkinsonian. Little is known about available health-economic parameters for multiple system atrophy, and it remains unclear if the current available data are sufficient to construct an early health technology assessment. This assessment considered (i) if data gaps can be minimised or cost-effectiveness modelling can be facilitated by conducting literature searches for disease analogues, (ii) if an early health technology assessment is feasible with the currently available data, and (iii) the potential for developing user-friendly model interfaces in rare diseases.Literature searches were conducted for economic evaluations and health-economic parameters (including costs, utilities, natural history of disease) for multiple system atrophy. The searches for disease analogues focussed on economic evaluations and showed a widespread use of functional or disability scales to inform model structures; we therefore used the unified multiple system atrophy rating scale part IV (global disability scale) to inform the model structure. Natural history of disease data were used to inform utilities and transition probabilities. Analyses of a hypothetical intervention were conducted from the perspective of the United Kingdom National Health Service with a cost-effectiveness threshold of £30,000 per quality-adjusted life year. The cost-effectiveness analysis was presented using a user-friendly interface in R Shiny, which provides stakeholders with an opportunity to explore results.Cost-effectiveness analyses were not identified for multiple system atrophy; however, two cost-of-illness, 20 quality-of-life, and nine natural history of disease studies were identified. Health-economic parameters were estimated from registry data, such as utilities and transition probabilities. A cost-effectiveness analysis was constructed for a hypothetical intervention despite evidence shortcomings, for example, aggregated cost data. An R Shiny app with a user-friendly interface was developed for stakeholders to change inputs and evaluate results.Literature searches for disease analogues proved useful for early modelling in multiple system atrophy, for example, to inform model structures, but surrogate data could only be used when sufficient granularity was available (e.g., micro costing). These findings suggest that early conceptual modelling can help identify data gaps and guide future evidence generation, such as selecting appropriate endpoints for natural history of disease studies. Cost-effectiveness results can be highly uncertain for rare diseases at these early stages and should be considered as part of an iterative modelling framework. Grand, Tobias Sydendal; Ren, Shijie; Thokala, Praveen; Zanigni, Stefano; Åström, Daniel Oudin; Bidani, Aroussi; Höglinger, Günter; Poewe, Werner; Krismer, Florian; Regnier, Stephane; Investigators, EMSA-SG Natural History Study

Forschungszentrum DZNE1d ago
New paper out: How alexithymia shapes functional networks: Insights from a general population study.: Krause, Elischa; Klinger-König, Johanna; Goerlich, Katharina S; et al.
European psychiatry Vol. 69, no. 1, p. e45 http://dlvr.it/TS5k8H | Please share #dzne #papers
How alexithymia shapes functional networks: Insights from a general population study. - DZNEPUB

Alexithymia is a multifaceted, transdiagnostic trait characterized by challenges in emotion processing. Affecting up to 10% in the general population, it represents a risk factor for various mental and physical health conditions. Recent neuroimaging studies have elucidated the neural substrates of alexithymia, providing initial insight into altered functional connectivity within key emotional, attentional, and interoceptive networks, potentially impairing emotion processing and everyday functioning. However, no large-scale study has yet confirmed these network alterations.Resting-state functional magnetic resonance imaging from 575 individuals (ages 29-60, 334 women) in the population-based SHIP-TREND cohort, using regions of interest covering major functional networks across the whole brain, was paired with the 20-item Toronto Alexithymia Scale (TAS-20) to investigate the signature of alexithymia. The analysis accounted for technical variables, sociodemographic factors, lifestyle, and current depressive symptoms.Higher TAS-20 scores were associated with altered functional connectivity within the frontoparietal network and between the dorsal attention and salience networks. Specifically, the subscale 'difficulties identifying feelings' was associated with functional alterations between and within attentional, salience, and sensorimotor networks, indicating a divergent pattern within the salience network.These findings underscore the widespread impact of alexithymia on brain networks involved in emotional attention, interoception, and somatosensory processing. Controlling for lifestyle factors, current depressive symptoms, and other health indicators supports the specificity of these patterns. This supports the view of alexithymia as a personality trait that affects large-scale network functioning, potentially hampering emotional regulation and self-awareness processes, contributing to mental and physical health risks. Krause, Elischa; Klinger-König, Johanna; Goerlich, Katharina S; Frenzel, Stefan; Bülow, Robin; Wielpütz, Mark Oliver; Völzke, Henry; Grabe, Hans J

Forschungszentrum DZNE3d ago
New paper out: Impact of lifestyle factors on quantitative motor and cognitive performance: insights from a longitudinal study on healthy ageing.: Zimmermann, Milan; Sünkel, Ulrike; Wurster, Isabel; et al.
GeroScience Vol. 48, no. 1, p. 1259 - 1275 http://dlvr.it/TS4Jyk | Please share #dzne #papers
Impact of lifestyle factors on quantitative motor and cognitive performance: insights from a longitudinal study on healthy ageing. - DZNEPUB

The process of ageing is extremely variable in progression and phenotypic features including significant variations in disease milestones, such as cognitive impairment, frailty, or recurrent falls. Our aim was to analyze the influence of lifestyle factors on motor and cognitive performance in a longitudinal ageing study in older people on healthy ageing. We conducted a longitudinal analysis in a cohort of 744 older participants (mean 70 years) over an 8-year period. Cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERADplus) test battery, including the Trail Making Test (TMT) for executive function. Gait performance was evaluated by measuring gait velocity. Dual-task performance was assessed by measuring gait velocity while checking boxes. Body Mass Index (BMI) was also recorded. Symptoms of depression were examined using Beck's Depression Inventory (BDI-II). We observed higher cognitive functions in individuals adhering to a high-frequency physical activity regimen and a resilient plant-based diet. Additionally, these individuals exhibited lower BDI-II scores and experienced mitigated cognitive decline. Participants who combined high physical activity, a high intake of plant-based foods, and extensive education-referred to as having a high 'successful ageing index' -maintained nearly constant CERADplus total scores over the 8-year period. Protective lifestyle factors are linked to better cognitive and motor performance and a slower decline in cognitive function, indicating healthy ageing. Since the factors diet and exercise are modifiable, adopting them may enhance cognitive performance and autonomy in older adults. Zimmermann, Milan; Sünkel, Ulrike; Wurster, Isabel; Lerche, Stefanie; Hobert, Markus A; Schulte, Claudia; von Thaler, Anna-Katharina; Berg, Daniela; Maetzler, Walter; Fallgatter, Andreas; Eschweiler, Gerhard W; Gasser, Thomas; Brockmann, Kathrin; Roeben, Benjamin

Forschungszentrum DZNE3d ago
New paper out: Emotion recognition in patients with mild cognitive impairment: The role of face processing and emotional intelligence.: Mahadevan, Rachana; Giesers, Naomi Kristin; Liman, Thomas; et al.
Journal of Alzheimer's disease Vol. 110, no. 1, p. 13872877251414969 http://dlvr.it/TS447x | Please share #dzne #papers
Emotion recognition in patients with mild cognitive impairment: The role of face processing and emotional intelligence. - DZNEPUB

BackgroundEmotion recognition ability is essential for social cognition, enabling humans to interpret and respond to emotion-related cues. However, so far, it is not known how underlying cognitive deficits, face processing and emotional intelligence are associated with emotion recognition, particularly in patients with mild cognitive impairment (MCI).ObjectiveTo examine emotion recognition performance in patients with MCI and the associations between emotion recognition, face processing, emotional interference, and emotional intelligence.Methods60 participants (patients with MCI = 30, healthy controls (HC) = 30), aged 50-86 years (M = 66.8, SD = 8.66), completed the Emotion Composite Task (ECT), Facial Composite Task (FCT), and Emotion Stroop Task. Emotional intelligence (EI) was assessed using the Trait Emotional Intelligence Questionnaire (TEIQUE).ResultsOverall, patients with MCI performed worse on the ECT than healthy controls (β = -0.36, p = 0.207, FDR p = 0.311), although this difference did not reach significance. Emotion-specific analysis showed that anger recognition was particularly impaired in patients with MCI (β = -0.86, p < 0.001). Better face processing ability was associated with better anger recognition (β = 0.28, p < 0.05), and higher EI with better overall emotion recognition (β = 0.62, p < 0.05).ConclusionsAlthough overall emotion recognition performance did not significantly differ between groups, patients with MCI showed selective impairments in recognizing anger. Face processing and emotional intelligence were associated with better emotion recognition, suggesting that patients with MCI who have stronger perceptual and socio-emotional skills preserve their emotion recognition abilities more effectively. Mahadevan, Rachana; Giesers, Naomi Kristin; Liman, Thomas; Witt, Karsten; Hildebrandt, Andrea; Roheger, Mandy

Forschungszentrum DZNE3d ago
New paper out: Reduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model.: Özkan, Burak; Ramge, Jan-Moritz; Wiesner, Diana; et al.
JCI insight Vol. 11, no. 5, p. e197475 http://dlvr.it/TS3qrq | Please share #dzne #papers
Reduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model. - DZNEPUB

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. Emerging evidence suggests manifestations beyond the neuromuscular system. Bone alterations are part of the ALS clinical picture; it remains unclear whether they are secondary to muscle denervation or due to an autonomous process. We investigated skeletal involvement in the SOD1(G93A) mouse model at presymptomatic (P45) and symptomatic (P110) stages through biomechanical and transcriptomic approaches. Three-point bending revealed significant reductions in femoral rigidity and maximum bending force in SOD1 mutants at P45, indicating early structural deficits. Micro-CT analysis demonstrated reduced trabecular bone mineral density and thickness at P45, with progressive trabecular loss and cortical thinning by P110. Histological examination revealed marked osteoblast loss at P45, suggesting impaired bone formation as the primary early mechanism. Transcriptomics of bulk bone and cultured osteoblasts from P45 mice identified dysregulation of bone differentiation, including downregulation of osteoblast differentiation genes and upregulation of negative regulators of ossification and increased cell senescence signatures. Unfolded protein response was upregulated in SOD1 osteoblasts. Immunohistochemistry confirmed the senescence phenotype with increased p16Ink4a level in SOD1 osteoblasts. These findings suggest that bone deterioration precedes overt motor symptoms and is linked to osteoblast premature senescence. Özkan, Burak; Ramge, Jan-Moritz; Wiesner, Diana; Scekic-Zahirovic, Jelena; Antonucci, Stefano; Nungeß, Sandra; Gebauer, Dorothea; Ignatius, Anita; Weishaupt, Jochen H; Haffner-Luntzer, Melanie; Roselli, Francesco

Show threadFabrizio MusacchioApr 2

@MaFu55 #CX3CR1 deficiency enhances microglial reactivity while limiting GB cell migration, and CSF1R inhibition also constrains #tumor microtube #plasticity. Together, the data place #microglia directly in the control of #glioblastoma invasion dynamics.

Huge congrats to Felix and all co-authors! 🥳

@dzne #DZNE

Fabrizio MusacchioMar 23

A great start to #BonnBrain26 🧠 today, highlighted by the excellent young investigator talks by Martin Pofah, Samuel Eckmann, Nicole Hoffmann, Carlo Castoldi, Karen Yu Chen Cheng, Carina Seidl, Jens-Bastian Eppler and Julia Schnermann 💫💪

#DZNE #BonnBrain @dzne